Vanadium has been shown to reproduced in vitro, most, if not all of the insulin actions. It has only been shown to normalise blood glucose in STZ-diabetic rats. In diabetic man, the only study available was done a century ago and showed that vanadium could decrease glycosuria. The present research proposal is a preliminary and feasibility study on the use of vanadium in the treatment of patients with NIDDM. Specifically, we will be studying the pharmacokinetics and the safety of vanadyl sulphate as well as its efficacy to improve the glycaemic control in type II diabetic patients. The safety parameters will include blood pressure, body weight, CBC, biochemistry profile including liver function test, urinalysis, microalbuminuria, and symptomatology questionnaire. The efficacy parameters will include fasting and postprandial plasma glucose, plasma insulin and plasma C-peptide, the fasting HbA1c and/or fructosamine and lipid profile. Vanadium will be measured by serum, urine and faeces to study the pharmacokinetics of the drug and the dose- related efficacy data. The study will be done in two (2) consecutive phases. The first phase will be an acute study where twenty-four (24) NIDDM subjects and twenty-four (24) control subjects will be given a single oral intake of vanadyl sulphate of 7.5 mg, 15 mg or 22.5 mg or placebo in a single-blind fashion and the various pharmacokinetic, safety and efficacy parameters will be followed for 24 hours in the hospital and then for one month as outpatient; its purpose is mainly to study the toxicity and the pharmacokinetics of vanadyl sulphate. The second phase will be a short term study where forty (40) NIDDM patients will be randomised in a double-blind fashion into one of the following four (4) groups; 7.5 mg TID, 15 mg TID, 22.5 mg TID or placebo TID for a two-month treatment period. Again the pharmacokinetics, the safety and the efficacy parameters will be followed throughout the 2-month treatment period and for one month after stopping the vanadyl; the purpose of this second phase is mainly to study the efficacy of vanadyl to improve glycaemic control. The studies will give us the following information: 1) it will tell us whether vanadyl sulphate can be tolerated by humans without major side effects or toxicity; 2) it will give us information on the absorption of the drug, the serum levels after a single-dose and after chronic administration at 3 dose levels and its elimination; and 3) it will tell us whether it is effective in improving glycaemic control in NIDDM patients. If, as we believe, it will be tolerated and effective, we will be able to plan long term clinical trial with vanadyl sulphate in NIDDM compared to other hypoglycaemic drugs as monotherapy, and taken in combination with other hypoglycaemic drug including insulin. More interestingly, we will be able to characterize the effects of vanadyl sulphate in healthy and diabetic man looking at the regulation of carbohydrate, lipid and protein metabolism. Furthermore, we will be able to extend these studies in patients with IDDM where vanadyl sulphate could, at least theoretically, replaced insulin injection.